In Japan having a hot and humid climatic property, measures against mycoses caused by pathogenic fungi are a particularly important pharmaceutical theme. Reoccurrence of such a disease is repeatedly caused by remaining living microbes even if the disease appears to have been perfectly cured. For example, summer is a season in which the disease easily reoccurs, and thus, repetitive treatments are required. Therefore, an antifungal agent having an excellent medicinal effect has been demanded. Further, simultaneously, mycoses include those which develop on hand and foot portions such as tinea pedis and tinea unguium, those which develop on the body skin such as tinea, and those which develop on the scalp such as seborrheic dermatitis, and there is also a demand for development of a versatile dosage form which can be applied to the respective portions.
As an antifungal agent having an excellent antifungal effect, for example, luliconazole, one of compounds represented by the general formula (1), has attracted attention as a medicament that allows a treatment period to be shortened (for example, see JP 09-100279 A and JP 02-275877 A). Such compounds are also useful for onychomycosis, and a formulation thereof for onychomycosis, which is a hydrogel-like formulation, is also already known (for example, see WO 03/105841). Thus, the compounds represented by the general formula (1) can be said to be excellent in antifungal property as well. However, the compounds represented by the general formula (1) are poorly-soluble in an aqueous medium in terms of solubility, and must be formulated by using a solubilizing agent. As a result, the control of a variation in the bioavailability of medicaments to be caused by such a solubilizing agent has been the single and greatest problem in a formulation study. In particular, in the case of allowing a cellulose-based thickener or the like to coexist for viscosity adjustment, the addition of such a cellulose-based thickener also has an action of enhancing a horny cell layer storage (hereinafter, also referred to as a storage or a retention of a medicament in the horny cell layer). Thus, in some cases, a variation in the compounding amount of such a thickener for viscosity adjustment has also caused a change in the pharmacodynamic property and a change in the bioavailability of a formulation. A medicine is always required to retain bioequivalence, and it can be said that the development of a system capable of compensating such a change in the pharmacodynamic property and of maintaining bioequivalence has been demanded for the formulation design of the compounds represented by the general formula (1).
Meanwhile, there has not been known any pharmaceutical composition for antifungal use containing: 1) one or more compounds selected from compounds represented by the general formula (1) below and physiologically acceptable salts thereof; 2) one or more compounds selected from polypropylene glycol, diesters of dibasic acids, triacetin, 2-ethyl-1,3-hexanediol, lauromacrogol, and polyoxyethylene-polyoxypropylene glycol; and 3) one or more compounds selected from glucono-δ-lactone, propylene glycol, glycerin, and lactic acid. Further, there has been no finding that a change in the bioavailability of the compounds represented by the general formula (1) due to a variation in the formulation components can be compensated by adopting such a composition.
It should be noted that, there are already known techniques of incorporating ingredients such as polypropylene glycol, diesters of dibasic acids, triacetin, 2-ethyl-1,3-hexanediol, lauromacrogol, polyoxyethylene-polyoxypropylene glycol, glucono-δ-lactone, propylene glycol, glycerin, or lactic acid into a pharmaceutical composition for antifungal use for the purpose of serving as an absorption accelerant, a pH stabilizer, or the like (for example, see JP 2004-529935 A, JP 2003-252798 A, JP 2004-529923 A, WO 96/011710, and WO 01/003742).
wherein X represents a halogen or hydrogen.
